Purinergic receptors and pannexin channels in the activation of innate immune cells of the choroid plexus

免疫反应是一个精心策划的生化级联反应，启动对入侵生物体或分子的系统反应。传统上，大脑一直被认为是一个具有免疫特权的器官，由于存在实质性的血脑屏障，它与血液循环隔离开来。然而，在脑室的水平上，脉络膜丛含有对分子和细胞具有高度渗透性的血管。目前尚不清楚脉络膜丛如何产生免疫特权屏障，但它似乎涉及一类独特的巨噬细胞样细胞，即网膜丛或Kolmer细胞。本研究计划旨在了解在全身免疫系统的背景下，神经丛细胞的细胞生理学。在三个特定目标中，我将研究负责神经丛细胞激活的离子通道和受体，确定神经丛细胞如何与脉络膜丛上皮细胞交流，并研究体内给予的全身免疫挑战如何改变神经丛细胞的急性反应。该研究计划将建立在实验室在pannexin-1离子通道生物学领域的专业知识和世界领先地位之上。

The immune response is an orchestrated biochemical cascade that initiates systemic responses to invasive organisms or molecules. Traditionally, the brain has been considered to be an immune privileged organ, remaining isolated from the circulation because of a substantial blood brain barrier. However, at the level of the brain ventricles, the choroid plexus contains blood vessels that are highly permeable to molecules and cells. It is not known how an immune privileged barrier is generated at the choroid plexus, but it appears to involve a unique class of macrophage-like cells, the epiplexus or Kolmer cells. This proposed research program aims to understand the cellular physiology of epiplexus cells in the context of the systemic immune system. In three specific Objectives, I will investigate the ion channels and receptors that are responsible for epiplexus cell activation, determine how epiplexus cells communicate with the epithelial cells of the choroid plexus, and investigate how systemic immune challenges, given in vivo, alter acute responses of epiplexus cells. The research program will build upon the lab's expertise and world leadership in the area of pannexin-1 ion channel biology. Our approach is unique and innovative, providing exciting opportunities for the training and development of highly qualified personnel. The work here will dramatically increase our understanding of how immune challenges contribute to brain barriers and identify the role of specific cell types and ion channels in this fundamental physiological mechanism.